DESCRIPTION, OVERALL (provided by applicant): The overarching goal of the George M. O'Brien Kidney Center at Yale is to facilitate translational and clinical research that will advance the prevention and treatment of kidney diseases. Major themes of the Center are the development and phenotyping of mouse models of renal dysfunction, the identification of simple and complex genetic causes of kidney disease in humans, and the bidirectional exchange of information between mouse and human disease models in order to advance knowledge of human kidney diseases. A critically important benefit of the Yale Center will be to provide renal investigators both at Yale and across the country with access to highly specialized services not otherwise routinely available to support their research. To this end, three Center Cores will be established whose specific objectives are to provide small animal physiology services to allow detailed characterization of renal function at the level of the tubule, the kidney, and the intact organism in normal animals and in animal models of renal injury and kidney disease;provide mouse genetics and cell line services to develop new animal models and kidney cell lines to elucidate the molecular mechanisms underlying the pathophysiology of kidney diseases;and provide human genetics and clinical research services to apply genetic and genomic technologies to the study of human kidney diseases. We have identified a research user base of 51 investigators, including 18 at outside institutions, who have expressed specific interest in using core services of the Yale Kidney Center. A Pilot and Feasibility Program will be established to provide initial project funding for young investigators, to attract new investigators into the field of kidney disease research, and to foster translational and clinical studies directly related to kidney diseases. In addition, an Enrichment Program will be established to promote interdisciplinary interactions and collaborations among renal investigators participating in the Center;facilitate the application of new technologies to kidney disease research;and provide an online index of resources developed in the Center (e.g. antibodies, transgenic mouse lines, cell lines) so that they can be made available to renal investigators both at Yale and other institutions. The Center will also include a Research Training Program to enhance the training of graduate students, medical students, and postdoctoral fellows in kidney disease research in general, and in the specialized methods provided by the Center Cores in particular.